Trial Outcomes & Findings for IVIg for Small Fiber Neuropathy With Autoantibodies TS-HDS and FGFR3 (NCT NCT03401073)
NCT ID: NCT03401073
Last Updated: 2023-09-13
Results Overview
Difference in intra-epidermal nerve fiber density between visits 1 and 8 will be measured. Intra-epidermal nerve fiber density is a quantitative measure of the number of nerve fibers per millimeter. The outcome is the number of nerve fibers measured at visit 8 minus the number of nerve fibers measured at visit 1. A positive value indicates that nerve fiber density has increased (a better outcome), a negative value indicates that the nerve fiber density has decreased (a worse outcome).
COMPLETED
PHASE2
20 participants
Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).
2023-09-13
Participant Flow
Potential research subjects were recruited from Beth Israel Deaconess Medical Center (BIDMC) (Boston, MA) and HonorHealth Neurology (Phoenix, AZ). All recruited subjects signed a consent form approved by the Institutional Review Boards of BIDMC and HonorHealth.
After signing an informed consent, study subjects underwent a detailed history, physical examination, laboratory studies, pain VAS scores, the Short-From 36 question health survey (SF-36), antibody measurement of TS-HDS and FGFR-3 and skin biopsy evaluation of nerve fiber density at the distal leg and proximal thigh using standard methodology. If participants did not meet criteria for the study after screening (based on inclusion and exclusion criteria), they were excluded.
Participant milestones
| Measure |
0.9% Sodium Chloride
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The placebo will consist of 0.9% Sodium Chloride per day over 2 days. Followed by 0.9% Sodium Chloride over 1 day every 3 weeks for a total of 6 treatments. Participants who are randomized to placebo will receive the same volume as they would if they were randomized to IVIG (i.e.: as if receiving IVIG at 2gm/kg) through a peripheral IV line.
0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
|
Intravenous Immunoglobulin
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. Treatment will consist of IVIG administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments
Intravenous immunoglobulin: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
9
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
0.9% Sodium Chloride
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The placebo will consist of 0.9% Sodium Chloride per day over 2 days. Followed by 0.9% Sodium Chloride over 1 day every 3 weeks for a total of 6 treatments. Participants who are randomized to placebo will receive the same volume as they would if they were randomized to IVIG (i.e.: as if receiving IVIG at 2gm/kg) through a peripheral IV line.
0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
|
Intravenous Immunoglobulin
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. Treatment will consist of IVIG administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments
Intravenous immunoglobulin: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
Baseline Characteristics
IVIg for Small Fiber Neuropathy With Autoantibodies TS-HDS and FGFR3
Baseline characteristics by cohort
| Measure |
0.9% Sodium Chloride
n=10 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The placebo will consist of 0.9% Sodium Chloride per day over 2 days. Followed by 0.9% Sodium Chloride over 1 day every 3 weeks for a total of 6 treatments. Participants who are randomized to placebo will receive the same volume as they would if they were randomized to IVIG (i.e.: as if receiving IVIG at 2gm/kg) through a peripheral IV line.
0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
|
Intravenous Immunoglobulin
n=10 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. Treatment will consist of IVIG administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments
Intravenous immunoglobulin: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
51.3 Years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
51.5 Years
STANDARD_DEVIATION 7.8 • n=7 Participants
|
51.4 Years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Intra-epidermal nerve fiber density
|
2.02 Fibers/mm
STANDARD_DEVIATION 1.49 • n=5 Participants
|
2.47 Fibers/mm
STANDARD_DEVIATION 1.83 • n=7 Participants
|
2.25 Fibers/mm
STANDARD_DEVIATION 1.66 • n=5 Participants
|
|
Pain score
|
5.5 units on a scale
STANDARD_DEVIATION 1.2 • n=5 Participants
|
6.9 units on a scale
STANDARD_DEVIATION 1.8 • n=7 Participants
|
6.2 units on a scale
STANDARD_DEVIATION 1.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).Population: The 17 study completers were analyzed as part of the final results.
Difference in intra-epidermal nerve fiber density between visits 1 and 8 will be measured. Intra-epidermal nerve fiber density is a quantitative measure of the number of nerve fibers per millimeter. The outcome is the number of nerve fibers measured at visit 8 minus the number of nerve fibers measured at visit 1. A positive value indicates that nerve fiber density has increased (a better outcome), a negative value indicates that the nerve fiber density has decreased (a worse outcome).
Outcome measures
| Measure |
0.9% Sodium Chloride
n=9 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The placebo will consist of 0.9% Sodium Chloride per day over 2 days. Followed by 0.9% Sodium Chloride over 1 day every 3 weeks for a total of 6 treatments. Participants who are randomized to placebo will receive the same volume as they would if they were randomized to IVIG (i.e.: as if receiving IVIG at 2gm/kg) through a peripheral IV line.
0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
|
Intravenous Immunoglobulin
n=8 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. Treatment will consist of IVIG administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments
Intravenous immunoglobulin: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
|
|---|---|---|
|
The Change in Nerve Fiber Density Between Visits 1 and 8.
|
0.5 fibers/mm
Standard Deviation 0.8
|
0.6 fibers/mm
Standard Deviation 0.6
|
SECONDARY outcome
Timeframe: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).The visual analog scale (VAS) of pain allows for quantification of neuropathic pain. The VAS pain scale depicts a line ranging from 0 (no pain) to 10 (worst possible pain). The scale is ordinal ranging from 0-10. The difference in pain between visit 1 and visit 8 (pain measured at visit 8 subtracted from the score at visit 1) is the range. Positive values indicate an increase in pain (worse outcome), negative values indicate an improvement in pain (better outcome).
Outcome measures
| Measure |
0.9% Sodium Chloride
n=9 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The placebo will consist of 0.9% Sodium Chloride per day over 2 days. Followed by 0.9% Sodium Chloride over 1 day every 3 weeks for a total of 6 treatments. Participants who are randomized to placebo will receive the same volume as they would if they were randomized to IVIG (i.e.: as if receiving IVIG at 2gm/kg) through a peripheral IV line.
0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
|
Intravenous Immunoglobulin
n=8 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. Treatment will consist of IVIG administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments
Intravenous immunoglobulin: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
|
|---|---|---|
|
The Change in Neuropathic Pain Severity Between Visits 1 and 8.
|
-1.7 units on a scale
Standard Deviation 0.9
|
-1.9 units on a scale
Standard Deviation 2.6
|
SECONDARY outcome
Timeframe: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).The Utah Early Neuropathy Scale (UENS) was developed specifically to detect and quantify early small-fiber sensory neuropathy and to recognize modest changes in sensory severity and distribution. The UENS scale ranges from 0 (no neuropathy) to 42 (severe small fiber neuropathy). The outcome measure is the UENS score from Visit 8 minus the UENS score at visit 1. The difference in the two scores indicates the change in neuropathy severity. A positive value indicates that neuropathy has worsened over the course of the study, a negative value indicates that neuropathy has improved over the course of the study.
Outcome measures
| Measure |
0.9% Sodium Chloride
n=9 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The placebo will consist of 0.9% Sodium Chloride per day over 2 days. Followed by 0.9% Sodium Chloride over 1 day every 3 weeks for a total of 6 treatments. Participants who are randomized to placebo will receive the same volume as they would if they were randomized to IVIG (i.e.: as if receiving IVIG at 2gm/kg) through a peripheral IV line.
0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
|
Intravenous Immunoglobulin
n=8 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. Treatment will consist of IVIG administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments
Intravenous immunoglobulin: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
|
|---|---|---|
|
2) The Difference in Change Between Quantified Utah Early Neuropathy Examination Scores, Between Treatment and Placebo Groups Between Visits 1 and 8.
|
-3.0 units on a scale
Standard Deviation 5.8
|
-1.8 units on a scale
Standard Deviation 3.9
|
Adverse Events
0.9% Sodium Chloride
Intravenous Immunoglobulin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
0.9% Sodium Chloride
n=10 participants at risk
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The placebo will consist of 0.9% Sodium Chloride per day over 2 days. Followed by 0.9% Sodium Chloride over 1 day every 3 weeks for a total of 6 treatments. Participants who are randomized to placebo will receive the same volume as they would if they were randomized to IVIG (i.e.: as if receiving IVIG at 2gm/kg) through a peripheral IV line.
0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
|
Intravenous Immunoglobulin
n=10 participants at risk
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. Treatment will consist of IVIG administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments
Intravenous immunoglobulin: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
|
|---|---|---|
|
Product Issues
Infusion reaction
|
90.0%
9/10 • Number of events 25 • 6 months
Adverse events captured at 3 week intervals or by interval phone calls for any acute changes in condition.
|
80.0%
8/10 • Number of events 22 • 6 months
Adverse events captured at 3 week intervals or by interval phone calls for any acute changes in condition.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place